Evaluation of Type 2 Diabetes Risk Variants (Alleles) in the Pashtun Ethnic Population of Pakistan

Asif Jan; Muhammad Saeed; Zakiullah; Rani Akbar; Hamayun Khan

doi:10.15605/jafes.037.S3

Authors

Asif Jan University of Peshawar, Pakistan https://orcid.org/0000-0003-3880-5579
Muhammad Saeed University of Peshawar, Pakistan https://orcid.org/0000-0001-9949-4327
Zakiullah University of Peshawar, Pakistan https://orcid.org/0000-0001-7932-9498
Rani Akbar Adul Wali Khan University Mardan, Pakistan
Hamayun Khan Islam College of Pharmacy, Gujranwala, Punjab, Pakistan

DOI:

https://doi.org/10.15605/jafes.037.S3

Keywords:

type 2 diabetes, risk variants, bioinformatics, whole exome sequencing, Pashtun population

Abstract

Objective. To evaluate the Type 2 Diabetes (T2D) risk variants in the Pashtun ethnic population of Khyber Pakhtunkhwa using nascent whole-exome sequencing (WES) to better understand the pathogenesis of this complex polygenic disorder.

Methodology. A total of 100 confirmed patients with T2D of Pashtun ethnicity were included in the study, DNA was extracted from whole blood samples, and paired-end libraries were prepared using the Illumina Nextera XT DNA library kit carefully following the manufacturer’s instructions. Illumina HiSeq 2000 was used to obtain sequences of the prepared libraries followed by bioinformatics data analysis.

Results. A total of n=11 pathogenic/likely pathogenic variants were reported in the CAP10, PAX4, IRS-2, NEUROD1, CDKL1 and WFS1. Among the reported variants CAP10/rs55878652 (c.1990-7T>C; p.Leu446Pro) and CAP10/rs2975766 (c.1996A>G; p.Ile666Val) identified were novel, and have not yet been reported for any disease in the database. The variants CAP10/rs7607759 (c.1510A>G, p.Thr504Ala), PAX4/rs712701 (c.962A>C; p.His321Pro), PAX4/ rs772936097 (c.748-3delT; p.Arg325Trp), IRS-2/rs1805097 (c.3170G>A; p.Gly1057Asp), NEUROD1/rs1801262 (c.133A>G; p.Thr45Ala), CDKL1/rs77152992 (c.1226C>T; p.Pro409Leu), WFS1/rs1801212 (c.997G>A; p.Val333Ile), WFS1/rs1801208 (c.1367G>A; p.Arg456His), and WFS1/rs734312 (c.1832G>A; p.Arg611His) are previously identified in other ethnic populations. Our study reconfirms the associations of these variants with T2D in the Pakistani Pashtun population.

Conclusion. In-silico analysis of exome sequencing data suggests a statistically substantial association of all (n=11)
identified variants with T2D in the Pashtun ethnic population. This study may serve as a foundation for performing
future molecular studies aimed at unraveling T2D associated genes.

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Author Biographies

Asif Jan, University of Peshawar, Pakistan

Department of Pharmacy

Muhammad Saeed, University of Peshawar, Pakistan

Professor, Department of Pharmacy

Zakiullah, University of Peshawar, Pakistan

Department of Pharmacy

Rani Akbar, Adul Wali Khan University Mardan, Pakistan

Department of Pharmacy

Hamayun Khan, Islam College of Pharmacy, Gujranwala, Punjab, Pakistan

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